Knowledge about the effects of prenatal cocaine exposure (PCE) on brain development, behavior and cognition in humans lags far behind that of other drugs of abuse. Evidence from animal studies suggests that PCE causes significant alterations in gray matter and white matter development with long-lasting implications for behavioral functioning. Human neuroimaging studies in children and adolescents with PCE to date have revealed no gross structural brain abnormalities;however, decreases in subcortical structure volumes and differences in the integrity of white matter tracts in the frontal lobe have been reported. Studies of neuropsychological functioning in children with PCE have yielded mixed results. Generally, children with PCE do not show significant decrements in overall cognitive abilities as measured by IQ tests but do show some problems with specific skills related to attention control, response inhibition, and other aspects of executive functioning. Our group has previously demonstrated significant relationships between frontal white matter development and executive functioning in a sample of children with PCE relative to those without. Compared to PCE, knowledge about the effects of postnatal cocaine exposure on brain development comes solely from animal models. These studies reveal alterations in neurotransmitter functioning that correlate with impulsive and aggressive behavior. In response to RA-DA-09-020 Secondary Data Analyses for Substance Abuse Research (R21/R33), we propose to use two datasets from a NIDA-funded longitudinal study of PCE that included prospective enrollment of participants, quantitative measures of drug exposures, excellent retention, and repeated collection of child hair samples to detect cocaine use among the youth. The two datasets, collected at ages 101/2 to 121/2 and ages 14 to 16, include high-resolution T1-weighted and diffusion tensor neuroimaging data, neuropsychological assessments, and standardized behavior reports. This multidisciplinary project brings together investigators from three universities with expertise in neuropsychology, imaging, neuroanatomy, prenatal drug abuse research, and statistics. Using advanced, state-of- the-art image analysis techniques including cortical pattern matching, tensor based morphometry and tract-based spatial statistics, this project promises to yield important scientific information about the effects of PCE and the combined effects of pre- and postnatal cocaine exposure on the structure and function of the developing human brain. PUBLIC HEALTH RELEVANCE: Although subtle effects of prenatal cocaine exposure on behavior and thinking abilities have been demonstrated, the literature considerably lags behind our understanding of the effects of alcohol and other drugs on brain development and behavior. This study will provide vital information regarding the long-term effects of prenatal cocaine exposure, as well as postnatal use, on brain development, cognition, and behavior in children and adolescents. Emphasis is placed on the use of novel, cutting edge, state-of-the-art structural image analysis tools in conjunction with sophisticated neuropsychological tests to better understand the effects of cocaine on the structure and function of the developing human brain.